Table 2 ∣.
Gene associations with cardiometabolic and other diseases at FDR Q-value < 0.01
| Trait | Gene | Carriers | Cases among carriers (%) |
Cases among noncarriers (%) |
OR [95% CI] | P-value | Ref |
|---|---|---|---|---|---|---|---|
| Known associations | |||||||
| Hypertrophic cardiomyopathy | MYBPC3 | 93 | 9 (9.68) | 211 (0.11) | 120.38 [55.94-231.86] | 2.39 x 10−16 | 65,66 |
| Heart failure | TTN | 1,858 | 121 (6.51) | 5,223 (2.63) | 2.64 [2.15-3.20] | 2.14 x 10−18 | 67,68 |
| Dilated cardiomyopathy | TTN | 1,741 | 38 (2.11) | 339 (0.17) | 12.20 [8.44-17.09] | 4.14 x 10−27 | 68 |
| Atrial fibrillation | TTN | 1,858 | 211 (11.36) | 12,066 (6.08) | 2.06 [1.75-2.40] | 8.23 x 10−18 | 19,57,69 |
| Ventricular arrhythmia | TTN | 1,858 | 47 (2.53) | 2,025 (1.02) | 2.45 [1.77-3.30] | 4.18 x 10−8 | 28 |
| Diabetes type 2 | GCK | 64 | 31 (48.44) | 14,576 (7.28) | 13.98 [8.33-23.42] | 1.80 x 10−19 | 70 |
| Chronic kidney disease | PKD1 | 51 | 24 (47.06) | 6,391 (3.19) | 40.33 [21.27-76.24] | 3.54 x 10−25 | 71-73 |
| Hypercholesterolemia | LDLR | 104 | 74 (71.15) | 42,725 (21.34) | 13.11 [8.28-21.26] | 3.53 x 10−31 | 74-76 |
| APOB | 247 | 6 (2.43) | 42,793 (21.39) | 0.08 [0.03-0.18] | 4.27 x 10−13 | 77 | |
| PCSK9 | 258 | 20 (7.75) | 42,779 (21.38) | 0.26 [0.15-0.42] | 2.78 x 10−8 | 78 | |
| Hypothyroidism | TSHR | 304 | 48 (15.79) | 14,049 (7.02) | 2.53 [1.79-3.49] | 2.34 x 10−8 | 79 |
| TG | 785 | 97 (12.36) | 14,000 (7.02) | 1.83 [1.45-2.28] | 3.18 x 10−7 | 80,81 | |
| Novel associations * | |||||||
| Diabetes type 2 | GIGYF1 | 55 | 16 (29.09) | 14,591 (7.29) | 5.61 [2.90-10.32] | 3.04 x 10−7 | |
| CCAR2 | 26 | 11 (42.31) | 14,596 (7.29) | 12.79 [5.63-28.44] | 5.43 x 10−8 | ||
| Supraventricular tachycardia | TTN | 1,858 | 46 (2.48) | 2,029 (1.02) | 2.40 [1.73-3.23] | 7.88 x 10−8 | |
| Mitral valve disease | TTN | 1,858 | 81 (4.36) | 3,817 (1.92) | 2.31 [1.80-2.91] | 4.74 x 10−11 | |
P-values were computed using the saddle point approximation and were obtained from logistic mixed effects models, adjusting for sex, age, sequencing batch, associated principal components (PCs) and a sparse kinship matrix. P-values shown are unadjusted for multiple testing. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from Firth’s regression models adjusting for sex, age, sequencing batch and associated PCs among unrelated individuals.
*
Novel indicates that rare variant associations were not reported prior to the release of UK Biobank exomes. Ref, references.